Febrile neutropenia






Russell E. Lewis
Associate Professor of Infectious Diseases
Department of Molecular Medicine
University of Padua


{{< fa solid envelope size=1x >}} russelledward.lewis@unipd.it
{{< fa brands github size=1x >}} https://github.com/Russlewisbo

Objectives

  • What are the most common infections associated with short versus prolonged neutropenia?

  • How does the presentation of skin, mucocutaneous lesions, abdominal pain or pneumonia change the infection differential diagnosis?

  • What are common empiric antimicrobial regimens used

Normal hematopoiesis

Chemotherapy-associated neutropenia

  • Virtually all antineoplastic impair proliferation of normal hematopoietic progenitor cells

    • Obliteration of the mitotic pool

    • Depletion of the marrow reserve

  • Antineoplastic drugs, glucocorticoids and irradiation also interfere with the function of non-proliferating granulocytes, resulting in:

    • Decreased chemotaxis

    • Diminished phagocytic capacity

    • Defective intracellular killing

  • Glucocorticoids seem to enhance granulocytopoiesis and mobilize the marginal and marrow pool reserve, but…

    • reduce accumulation of granulocytes at site of infection (reduced adherence)

    • diminished chemotactic activity

    • decreased phagocytosis and intracellular killing

Immunity and innate immune cells

Source Molecules Active against

Polymorphonuclear leukocytes (PMNs)

  • 1 granules

  • Specific granules

Lysozyme, myeloperoxidase, defensins, BPI, lactoferrin

Bacteria, fungi
(with H2O2)

Bacteria, fungi

Macrophages

Similar to PMN but no myeloperoxidase

Nitric oxide

Arginase

Intracellular pathogens
(depletes arginine)
Eosinophil

Cationic proteins

Major basic protein

Peroxidase

Worms (extracellular)
Natural killing cells

Perforins

Granzymes

Viral or bacterial infected cells

Quantitative relationship of neutropenia with infection risk

Clinical signs if infection are muted in neutropenic patients


% of patients who have a neutrophil count/mm3 of:


Signs and Symptoms <100 101-1000 >1000
Fever 98 90 76
Fluctuance 6 36 52
Fissure or ulceration 21 42 54
Exudate 11 64 91
Purulent sputum 8 67 84
Pyuria 11 63 97

Model of mucosal barrier injury

Which bacterial pathogens translocate?

Severity of mucositis

WHO toxicity scale

References


Basile D, Di Nardo P, Corvaja C, Garattini SK, Pelizzari G, Lisanti C, et al. Mucosal Injury during Anti-Cancer Treatment: From Pathobiology to Bedside. Cancers 2019;11:857. https://doi.org/10.3390/cancers11060857.
Gerald P. Bodey, Bodey GP, Buckley M, Sathe YS, Freireich EJ, Freireich EJ. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Annals of Internal Medicine 1966;64:328–40. https://doi.org/10.7326/0003-4819-64-2-328.
Sickles EA, Greene WH, Wiernik PH. Clinical presentation of infection in granulocytopenic patients. Archives of Internal Medicine 1975;135:715–9.